Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines |
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Authors: | Dziadek Sebastian Kunz Horst |
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Affiliation: | Institut für Organische Chemie, Johannes-Gutenberg-Universit?t Mainz, Duesbergwerg 10-14, D-55128 Mainz, Germany. |
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Abstract: | In contrast to normal cells, the glycoprotein profile on epithelial tumor cells is distinctly altered. Due to an incomplete formation of the glycan side-chains resulting from a premature sialylation, additional peptide epitopes become accessible to the immune system in mucin-type glycoproteins on tumor cells. These tumor-associated structure alterations constitute the basis for a selective immunological attack on cancer cells. For the construction of immunostimulating antigens, glycopeptide partial structures from the mucins MUC1 and MUC4 carrying the tumor-associated sialyl-T(N), alpha2,6-sialyl-T and alpha2,3-sialyl-T antigens have been synthesized. Employing different linkers such as the allylic HYCRON or the fluoride-sensitive PTMSEL anchor, the antigenic glycopeptide structures were constructed on the solid phase utilizing pre-assembled glycosyl amino acid building blocks prepared in solution by convergent chemical or chemoenzymatic strategies. The proliferation of cytotoxic T cells has been induced applying a construct composed of a sialyl-T(N) MUC1-glycopeptide conjugated with a tetanus toxin T cell peptide epitope. |
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Keywords: | mucins glycopeptide synthesis tumor‐associated antigens sialyl‐TN/T antigens solid‐phase synthesis |
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